Glaucoma is the leading cause of irreversible blindness worldwide, affecting approximately 70 million people. By 2000, 2.2 million Americans had been diagnosed with glaucoma, and this number is estimated to reach 3.4 million by 2020. Primary open angle glaucoma (POAG) is a spectrum of disease causing vision loss which is associated with progressive and irreversible degeneration of nerve cells in the retina. The prevalence of POAG is 3% among those of Asian ancestry, 6% among Caucasians, and 16% among those of African ancestry age 70 and older. POAG appears almost 10 years earlier and progresses more quickly in African Americans (AAs), making it the leading cause of irreversible blindness in this population. Genetics are known to play a role in this disease~ however, POAG genetics are complex, and many risk factors are involved. This proposal represents the first large population study specifically evaluating AAs for genetic risk factors. In order to examine AAs for POAG risk factors, a genome wide association study (GWAS) will be performed. GWAS is a method that detects genetic variants in a large population to determine if any variants are associated with a disease or trait. The proposed GWAS will generate data on these variants in 17,000 AAs, 2,000 with POAG and 15,000 controls. This experimental approach will identify genes associated with POAG in AAs, who disproportionately suffer from more severe forms of this disease. Many different clinical traits are associated with POAG, and investigation of clinica determinants of this diagnosis will be correlated with genetic data. Collaborations with other institutions that have explored this approach in other populations will be used to further enhance the data set. In addition to the GWAS, the portions of DNA responsible for coding proteins will be specifically examined, since abnormal proteins are associated with disease susceptibility, progression, and severity. Genetic risk factors for POAG have been identified in other populations. The relevance of these known risk factors, along with new risk factors that emerge from the proposed GWAS investigation, will be evaluated for Americans of African ancestry. The ultimate goal of the Primary Open Angle African-American Glaucoma Genetics Study (POAAGG) is to facilitate the development of rational, targeted screening, diagnosis and eventually novel treatments for AA POAG.